Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.

Abstract

Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 microg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure.

Department

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Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0011056

Publication Info

Chen, Benny J, Divino Deoliveira, Ivan Spasojevic, Gregory D Sempowski, Chen Jiang, Kouros Owzar, Xiaojuan Wang, Diane Gesty-Palmer, et al. (2010). Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates. PLoS One, 5(6). p. e11056. 10.1371/journal.pone.0011056 Retrieved from https://hdl.handle.net/10161/4547.

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Scholars@Duke

Chen

Jun Chen

Professor of Medicine
Spasojevic

Ivan Spasojevic

Associate Professor in Medicine
Owzar

Kouros Owzar

Professor of Biostatistics & Bioinformatics

cancer pharmacogenomics
drug induced neuropathy, neutropenia and hypertension
statistical genetics
statistical methods for high-dimensional data
copulas
survival analysis
statistical computing

Gesty-Palmer

Diane Gesty-Palmer

Adjunct Assistant Professor in the Department of Medicine

Dr. Gesty-Palmer is an Assistant Professor in the Department of Medicine and Division of Endocrinology and Metabolism. Her laboratory principally examines G protein-coupled receptor signaling mechanisms in bone metabolism with emphasis on parathyroid hormone (PTH) receptor biased agonism. These studies explore novel mechanisms of PTH receptor signaling and the contributions of β-arrestin to modulate bone formation and bone resorption. Her work has recently shown that β-arrestin, classically thought to turn off G protein signaling, activates a distinct G protein-independent signaling mechanism to stimulate bone formation. Examination of β-arrestin mediated signaling events may provide novel therapeutic targets for the treatment of metabolic bone diseases such as osteoporosis. Dr. Gesty-Palmer is the recipient of a BIRCWH Scholar Award for Interdisciplinary Research in Women’s Health in 2006 and an Arthritis Foundation Investigator Award in 2007.

Chao

Nelson Jen An Chao

Donald D. and Elizabeth G. Cooke Cancer Distinguished Research Professor

My research interests are in two broad areas, clinical hematopoietic stem cell and cord blood transplantation and in the laboratory studies related to graft vs. host disease and immune reconstitution. On the clinical side we are currently conducting approximately 50 different clinical protocols ranging from preparatory regimens, supportive care studies and disease specific protocols. Most of these clinical studies are centered around studies of the sources of stem cells and the methods to improve the long term outcome. There are exploratory protocols for novel therapies such as dendritic cell therapy for several malignancies, antiangiogenesis therapy, graft engineering to prevent graft-versus-host disease and antigen specific T cells or non specific NK cells to prevent relapse. Moreover a strong focus of the program is to develop cord-blood transplantation for adult patients with hematologic malignancies. The laboratory studies center on understanding the immunological events that occur with graft-vs-host disease and methods to prevent this disease. The current efforts focus on understanding murine reconstitution following transplantation, use of a peptide polymer to block MHC class II recognition of minor histocompatibility antigens, use of T cell engineering to prevent graft-versus-host disease at the same time preserving a graft-versus-malignancy effect.

For more information see http://ed-media.mc.duke.edu/BMT.nsf


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